Clinical Developments and Challenges in Treating FGFR2-Driven Gastric Cancer.

Recent advances in the treatment of gastric cancer (GC) with chemotherapy, immunotherapy, anti-angiogenic therapy and targeted therapies have yielded some improvement in survival outcomes; however, metastatic GC remains a lethal malignancy and amongst the leading causes of cancer-related mortality worldwide. Importantly, the ongoing molecular characterisation of GCs continues to uncover potentially actionable molecular targets. Among these, aberrant FGFR2-driven signalling, predominantly arising from amplification, occurs in approximately 3-11% of GCs.

Discovery of potent small-molecule inhibitors of lipoprotein(a) formation.

Lipoprotein(a) (Lp(a)), an independent, causal cardiovascular risk factor, is a lipoprotein particle that is formed by the interaction of a low-density lipoprotein (LDL) particle and apolipoprotein(a) (apo(a)). Apo(a) first binds to lysine residues of apolipoprotein B-100 (apoB-100) on LDL through the Kringle IV (K) 7 and 8 domains, before a disulfide bond forms between apo(a) and apoB-100 to create Lp(a) (refs. ).

Multinational experience with next-generation sequencing: opportunity to identify transthyretin cardiac amyloidosis and Fabry disease.

Background: Sarcomeric hypertrophic cardiomyopathy (HCM) must be differentiated from phenotypically similar conditions because clinical management and prognosis may greatly differ. Patients with unexplained left ventricular hypertrophy require an early, confirmed genetic diagnosis through diagnostic or predictive genetic testing. We tested the feasibility and practicality of the application of a 17-gene next-generation sequencing (NGS) panel to detect the most common genetic causes of HCM and HCM phenocopies, including treatable phenocopies, and report detection rates.

Assessing contemporary Arctic habitat availability for a woolly mammoth proxy.

Interest continues to grow in Arctic megafaunal ecological engineering, but, since the mass extinction of megafauna ~ 12-15 ka, key physiographic variables and available forage continue to change. Here we sought to assess the extent to which contemporary Arctic ecosystems are conducive to the rewilding of megaherbivores, using a woolly mammoth (M. primigenius) proxy as a model species.

Percutaneous Balloon-Expandable Stent Implantation to Treat Transverse Aortic Arch Obstruction: Medium- to Long-Term Outcomes of a Retrospective Multicenter Study.

Background: Transverse aortic arch obstruction is a challenging lesion for which stent implantation provides a potentially important alternate therapy. The objectives were to evaluate the technical, procedural, and medium-to-long-term clinical outcomes of percutaneous stent implantation of transverse aortic arch obstruction.

Methods: This is a retrospective, multicenter study of transverse aortic arch stent implantation.

Analysis of Player Performance and Financial Costs Associated With Implementation of an Updated National Hockey League Concussion Protocol: A Retrospective Comparative Study.

Background: An updated National Hockey League (NHL) concussion protocol (NHLCP) was established in the 2016-2017 season to mitigate the negative outcomes of sport-related concussions. However, few studies on the effects of implementing the NHLCP have been performed.

Purpose: To define concussion incidence and investigate differences in NHL player performance after a concussion during periods before and after NHLCP implementation and assess the financial impact on NHL teams associated with NHLCP implementation.

Brain Arteriovenous Malformation In Vitro Model for Transvenous Embolization Using 3D Printing and Real Patient Data.

Background And Purpose: Transvenous embolization has emerged as a novel technique for treating selected brain AVMs with high reported occlusion rates. However, it requires anatomic and technical skills to be successful and to ensure patient safety. Therefore, training and testing are essential for preparing clinicians to perform these procedures.

Cost-utility analysis of TAVI compared with surgery in patients with severe aortic stenosis at low risk of surgical mortality in the Netherlands.

Background: There is growing evidence to support the benefits of transcatheter aortic valve implantation (TAVI) over surgical aortic valve replacement (SAVR) in patients with symptomatic severe aortic stenosis (sSAS) who are at high- or intermediate-risk of surgical mortality. The PARTNER 3 trial showed clinical benefits with SAPIEN 3 TAVI compared with SAVR in patients at low risk of surgical mortality. Whether TAVI is also cost-effective compared with SAVR for low-risk patients in the Dutch healthcare system remains uncertain.

Discovery of GLPG2737, a Potent Type 2 Corrector of CFTR for the Treatment of Cystic Fibrosis in Combination with a Potentiator and a Type 1 Co-corrector.

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) protein. This epithelial anion channel regulates the active transport of chloride and bicarbonate ions across membranes. Mutations result in reduced surface expression of CFTR channels with impaired functionality.

Vigorous vs. moderate exercise to improve glucose metabolism in inactive women with polycystic ovary syndrome and insulin resistance: a pilot randomized controlled trial of two home-based exercise routines.

Objective: To study the impact of vigorous vs. moderate exercise on metabolic parameters in polycystic ovary syndrome (PCOS).

Design: Randomized controlled trial.

An Analysis of Solicitations From Predatory Journals in Ophthalmology.

Purpose: To evaluate trends associated with email communication from potentially predatory publishers to faculty in ophthalmology.

Design: Cross-sectional study METHODS: Ophthalmologists (n = 14) from various subspecialties and institutions were recruited to participate. Participants identified unsolicited emails that they had received originating from publishers in May 2021.

Disease progression strikingly differs in research and real-world Parkinson's populations.

Characterization of Parkinson's disease (PD) progression using real-world evidence could guide clinical trial design and identify subpopulations. Efforts to curate research populations, the increasing availability of real-world data, and advances in natural language processing, particularly large language models, allow for a more granular comparison of populations than previously possible. This study includes two research populations and two real-world data-derived (RWD) populations.

Lysholm and KOOS QoL Demonstrate High Responsiveness in Patients Undergoing Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis of Randomized Clinical Trials.

Background: There have been a large number of patient-reported outcome measures (PROMs) used to assess outcomes after anterior cruciate ligament (ACL) reconstruction (ACLR).

Purpose/hypothesis: The purpose was to determine which PROMs are being commonly used in randomized clinical trials (RCTs) to assess patients undergoing ACLR and to compare the responsiveness between them. It was hypothesized that the International Knee Documentation Committee (IKDC) score would be the most commonly used and responsive PROM among patients undergoing ACLR.

Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial.

For patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance-which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11/LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment-and developing effective therapies to overcome them, remains an unmet need.

Molecular simulation approaches to probing the effects of mechanical forces in the actin cytoskeleton.

In this article we give our perspective on the successes and promise of various molecular and coarse-grained simulation approaches to probing the effect of mechanical forces in the actin cytoskeleton.

Anterior Cruciate Ligament Hybrid Remnant Preservation Reconstruction Demonstrates Equivalent Patient-Reported Outcomes and Complications as Traditional Anterior Cruciate Ligament Reconstruction After 1 Year.

Purpose: To compare the outcomes of anterior cruciate ligament (ACL) Hybrid Remnant Preservation Reconstruction (HRPR) with traditional anterior cruciate ligament reconstruction (ACLR) and determine differences in patient-reported outcomes, range of motion (ROM), and complications after 12 months.

Methods: A retrospective cohort study of patients undergoing ACLR by a single surgeon from December 2020 to January 2022 was conducted. Patients undergoing ACL-HRPR were compared with control patients undergoing traditional ACLR with bone-patellar tendon-bone autograft.

Determinants and Clinical Relevance of Iodine Contrast Extravasation after Endovascular Thrombectomy: A Dual-Energy CT Study.

Background And Purpose: Iodine contrast extravasation (ICE) is common in patients with acute ischemic stroke (AIS) after endovascular-thrombectomy (EVT). The aim of our study was to evaluate the incidence of ICE assessed by dual-energy CT (DECT), its determinants, and associations with clinical outcome.

Materials And Methods: We retrospectively examined imaging parameters and clinical factors from consecutive patients with AIS treated with EVT who had a DECT 24 hours thereafter, identified at a single academic center.

Plasma VEGFA and PGF impact longitudinal tau and cognition in preclinical Alzheimer's disease.

Vascular dysfunction is increasingly recognized as an important contributor to the pathogenesis of Alzheimer's disease. Alterations in vascular endothelial growth factor (VEGF) pathways have been implicated as potential mechanisms. However, the specific impact of VEGF proteins in preclinical Alzheimer's disease and their relationships with other Alzheimer's disease and vascular pathologies during this critical early period remain to be elucidated.

What Do Patients Encounter When Searching Online About Meniscal Surgery? An Analysis of Internet Trends.

Background: Many patients use the internet to learn about their orthopaedic conditions and find answers to their common questions. However, the sources and quality of information available to patients regarding meniscal surgery have not been fully evaluated.

Purpose: To determine the most frequently searched questions associated with meniscal surgery based on question type and topic, as well as to assess the website source type and quality.

Temporal Variability of the Dominant Fecal Microbiota in Healthy Adult Cats.

While shifts in gut microbiota have been studied in diseased states, the temporal variability of the microbiome in cats has not been widely studied. This study investigated the temporal variability of the feline dysbiosis index (DI) and the abundance of core bacterial groups in healthy adult cats. The secondary aim was to evaluate the relationship between the fecal abundance of and the fecal concentrations of unconjugated bile acids.

Genome-wide association identifies novel ROP risk loci in a multiethnic cohort.

We conducted a genome-wide association study (GWAS) in a multiethnic cohort of 920 at-risk infants for retinopathy of prematurity (ROP), a major cause of childhood blindness, identifying 1 locus at genome-wide significance level (p < 5×10) and 9 with significance of p < 5×10 for ROP ≥ stage 3. The most significant locus, rs2058019, reached genome-wide significance within the full multiethnic cohort (p = 4.96×10); Hispanic and European Ancestry infants driving the association.